doi:

DOI: 10.3724/SP.J.1141.2013.02059

Zoological Research (动物学研究) 2013/34:2 PP.59-69

Tree shrews under the spot light: emerging model of human diseases


Abstract:
Animal models are indispensible in biomedical research and have made tremendous contributions to answer fundamental questions on human biology, disease mechanisms, and to the development of new drugs and diagnostic tools. Due to the limitations of rodent models in translational medicine, tree shrews (Tupaia belangeri chinensis), the closest relative of primates, have attracted increasing attention in modeling human diseases and therapeutic responses. Here we discuss the recent progress in tree shrew biology and the development of tree shrews as human disease models including infectious diseases, metabolic diseases, neurological and psychiatric diseases, and cancers. Meanwhile, the current problems and future perspectives of the tree shrew model are explored.

Key words:Tree shrew,Experimental animals,Fundamental biology,Animal models of human diseases

ReleaseDate:2015-04-16 19:34:16



Adkins RM, Honeycutt RL. 1991. Molecular phylogeny of the superorder archonta. Proc Natl Acad Sci USA, 88(22): 10317-10321.

Amako Y, Tsukiyama-Kohara K, Katsume A, Hirata Y, Sekiguchi S, Tobita Y, Hayashi Y, Hishima T, Funata N, Yonekawa H, Kohara M. 2010. Pathogenesis of hepatitis C virus infection in Tupaia belangeri. J Virol, 84(1): 303-311.

Brack M. 1998. Spontaneous tumours in tree shrews (Tupaia belangeri): population studies. J Comp Pathol, 118(4): 301-316. Brack M, Schwartz P, Heinrichs T, Schultz M, Fuchs E. 1996. Tumors of the respiratory tract observed at the German Primate Center, 1978-1994. J Med Primatol, 25(6): 424-434.

Cao J, Yang, EB, Su JJ, Li Y, Chow P. 2003. The tree shrews: adjuncts and alternatives to primates as models for biomedical research. J Med Primatol, 32(3): 123-130.

Chayama K, Hayes CN, Hiraga N, Abe H, Tsuge M, Imamura M. 2011. Animal model for study of human hepatitis viruses. J Gastroenterol Hepatol, 26(1): 13-18.

Chen J, Dai JJ, Sun XM. 2008. Advances in the use of tree shrews as animal models for hepatitis research. Chn J Com Med, 18(2): 59-62. [陈瑾, 代解杰, 孙晓梅. 2008. 树鼩肝炎动物模型的研究进展. 中国比较医学杂志, 18(2): 59-62.]

Chen SY, Xu L, Lü LB, Yao YG. 2011. Genetic diversity and matrilineal structure in Chinese tree shrews inhabiting Kunming, China. Zool Res, 32(1): 17-23. [陈仕毅, 许凌, 吕龙宝, 姚永刚. 2011. 昆明城郊中国树鼩群体线粒体DNA遗传多样性. 动物学研究, 32(1): 17-23.]

Collins PM, Tsang WN, Metzger JM. 1984. Influence of stress on adrenocortical function in the male tree shrew (Tupaia belangeri). Gen Comp Endocrinol, 55(3): 450-457.

Dolgin E. 2011. The murine candidate. Nature, 474(7350): S14-S15.

Dyson A, Singer M. 2009. Animal models of sepsis: why does preclinical efficacy fail to translate to the clinical setting?. Crit Care Med, 37(1): S30-S37.

Elliot OS, Elliot MW, Lisco H. 1966. Breast cancer in a tree shrew (Tupaia glis). Nature, 211(5053): 1105.

Fan Y, Huang ZY, Cao CC, Chen CS, Chen YX, Fan DD, He J, Hou HL, Hu L, Hu XT, Jiang XT, Lai R, Lang YS, Liang B, Liao SG, Mu D, Ma YY, Niu YY, Sun XQ, Xia JQ, Xiao J, Xiong ZQ, Xu L, Yang L, Zhang Y, Zhao W, Zhao XD, Zheng YT, Zhou JM, Zhu YB, Zhang GJ, Wang J, Yao YG. 2012. Genome of the Chinese tree shrew, a rising model animal genetically related to primates. Nat Commun, DOI: 10.1038/ncomms2416

Frost MR, Norton TT. 2012. Alterations in protein expression in tree shrew sclera during development of lens-induced myopia and recovery. Invest Ophthalmol Vis Sci, 53(1): 322-336.

Fuchs E. 2005. Social stress in tree shrews as an animal model of depression: an example of a behavioral model of a CNS disorder. CNS Spectr, 10(3): 182-190.

Fuchs E, Schumacher M. 1990. Psychosocial stress affects pineal function in the tree shrew (Tupaia belangeri). Physiol Behav, 47(4): 713-717.

Fuchs E, Flugge G. 2002. Social stress in tree shrews: effects on physiology, brain function, and behavior of subordinate individuals. Pharmacol Biochem Behav, 73(1): 247-258.

Glebe D, Aliakbari M, Krass P, Knoop EV, Valerius KP, Gerlich WH. 2003. Pre-S1 antigen-dependent infection of Tupaia hepatocyte cultures with human hepatitis B virus. J Virol, 77(17): 9511-9521.

Goldstein B, Giroir B, Randolph A. 2005. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med, 6(1): 2-8.

Gould E, McEwen BS, Tanapat P, Galea LAM, Fuchs E. 1997. Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci, 17(7): 2492-2498.

Hallstrom BM, Janke A. 2010. Mammalian evolution may not be strictly bifurcating. Mol Biol Evol, 27(12): 2804-2816.

Han JB, Zhang GH, Duan Y, Ma JP, Zhang XH, Luo RH, Lü LB, Zheng YT. 2011. Sero-epidemiology of six viruses natural infection in Tupaia belangeri chinensis. Zool Res, 32(1): 11-16. [韩建保, 张高红, 段勇, 马建平, 张喜鹤, 罗荣华, 吕龙宝, 郑永唐. 2011. 中缅树鼩自然感染六种病毒的血清流行病学. 动物学研究, 32(1): 11-16.]

Hofmann W, Möller P, Schwaier A, Flügel RM, Zöller L, Darai G. 1981. Malignant tumours in Tupaia (tree shrew). J Med Primatol, 10(2-3): 155-163.

Hotchkiss RS, Karl IE. 2003. Medical progress: the pathophysiology and treatment of sepsis. New Engl J Med, 348(2): 138-150.

Ishiko S, Yoshida A, Mori F, Abiko T, Kitaya N, Kojima M, Saito K. 1997. Early ocular changes in a tree shrew model of diabetes. J Jpn Ophthalmol Soc, 101: 19-23.

Jane?ka JE, Miller W, Pringle TH, Wiens F, Zitzmann A, Helgen KM, Springer MS, Murphy WJ. 2007. Molecular and genomic data identify the closest living relative of primates. Science, 318(5851): 792-794.

Jöhren O, Flügge G, Fuchs E. 1994. Hippocampal glucocorticoid receptor expression in the tree shrew: regulation by psychosocial conflict. Cell Mol Neurobiol, 14(3): 281-296.

Li QF, Ding MQ, Wang H, Mao Q, Wu CQ, Zheng H, Gu CH, Wang YM. 1995. The infection of hepatitis D virus in adult Tupaia. Nat Med J Chn, 75(10): 611-613. [李奇芬, 丁明权, 王洪, 毛青, 吴纯清, 郑红, 顾长海, 王宇明. 1995. 树鼩感染丁型肝炎病毒的实验研究. 中华医学杂志, 75(10): 611-613. ]

Li RX, Xu W, Wang Z, Liang B, Wu JR, Zeng R. 2012. Proteomic characteristics of the liver and skeletal muscle in the Chinese tree shrew (Tupaia belangeri chinensis). Protein Cell, 3(9): 691-700.

Li SA, Lee WH, Zhang Y. 2012. Two bacterial infection models in tree shrew for evaluating the efficacy of antimicrobial agents. Zool Res, 33(1): 1-6.

Li SQ, Meng Q, Zhang L. 1999. Experimental therapy of a platelet-activating factor antagonist (ginkgolide B) on photochemically induced thrombotic cerebral ischaemia in tree shrews. Clin Exp Pharmacol Physiol, 26(10): 824-825.

Li Y, Su JJ, Yang C, Cao J, Ou C, Liang L, Yang F, Wang Q. 2011. Progress on establishment of tree shrew (Tupaia) chronic infection with HBV in vivo. Zool Res, 32(1): 104-108. [李瑗, 苏建家, 杨春, 曹骥, 欧超, 梁亮, 杨芳, 王琦. 2011. 乙型肝炎病毒树鼩体内慢性感染模型的研究历程和展望. 动物学研究, 32(1): 104-108.]

Li Y, Su JJ, Qin LL, Egner PA, Wang JS, Groopman JD, Kensler TW, Roebuck BD. 2000. Reduction of aflatoxin B1 adduct biomarkers by oltipraz in the tree shrew (Tupaia belangeri chinensis). Cancer Lett, 154(1): 79-83.

Li Y, Qin X, Cui JF, Dai Z, Kang XN, Yue HY, Zhang Y, Su JJ, Cao J, Ou C, Yang C, Duan XX, Yue HF, Liu YK. 2008. Proteome analysis of aflatoxin B1-induced hepatocarcinogenesis in tree shrew (Tupaia belangeri chinensis) and functional identification of candidate protein peroxiredoxin II. Proteomics, 8(7): 1490-1501.

Liang L, Li Y, Yang C, Cao J, Su JJ, Chen MW, Ban KC, Ou C, Duan XX, Yue HF. 2006. Perinatal and young tree shrews infected with human hepatitis B virus. Chn J Zoon, 22(8): 792-795. [梁亮, 李瑗, 杨春, 曹骥, 苏建家, 陈茂伟, 班克臣, 欧超, 段小娴, 岳惠芬. 2006. 用人工繁育的围生期和幼年树鼩感染人乙型肝炎病毒的初步研究. 中国人兽共患病学报, 22(8): 792-795.]

Lindblad-Toh K, Garber M, Zuk O, Lin MF, Parker BJ, Washietl S, Kheradpour P, Ernst J, Jordan G, Mauceli E, Ward LD, Lowe CB, Holloway AK, Clamp M, Gnerre S, Alfoldi J, Beal K, Chang J, Clawson H, Cuff J, Di Palma F, Fitzgerald S, Flicek P, Guttman M, Hubisz MJ, Jaffe DB, Jungreis I, Kent WJ, Kostka D, Lara M, Martins AL, Massingham T, Moltke I, Raney BJ, Rasmussen MD, Robinson J, Stark A, Vilella AJ, Wen JY, Xie XH, Zody MC, Worley KC, Kovar CL, Muzny DM, Gibbs RA, Warren WC, Mardis ER, Weinstock GM, Wilson RK, Birney E, Margulies EH, Herrero J, Green ED, Haussler D, Siepel A, Goldman N, Pollard KS, Pedersen JS, Lander ES, Kellis M, Inst B, Med BC, Univ W. 2011. A high-resolution map of human evolutionary constraint using 29 mammals. Nature, 478(7370): 476-482.

Liu XH, Yao YG. 2013. Characterization of 12 polymorphic microsatellite markers in the Chinese tree shrew (Tupaia belangeri chinensis). Zool Res, 34 (E2):E63-E69.

Liu Z, Mao Q, Wang YM, Li QF. 1998. An experimental study on infection of hepatitis C virus in adult Tupaiae. J Third Mili Med Univ, 12(6): 472-475. [刘志, 毛青, 王宇明, 李奇芬. 1998. 丙型肝炎病毒感染成年树鼩的实验研究. 第三军医大学学报, 12(6): 472-475.]

Lucassen PJ, Fuchs E, Czeh B. 2004. Antidepressant treatment with tianeptine reduces apoptosis in the hippocampal dentate gyrus and temporal cortex. Biol Psychiatry, 55(8): 789-796.

Ma XT, Li FL, Jiang HJ, Lee WH, Zhang Y, Du TY. 2011. Detection and comparison of physiological indexes in the wild and laboratory tree shrew. Zool Res, 32(1): 4-10. [马旭通, 李福林, 蒋宏君, 李文辉, 张云, 杜廷义. 2011. 野生和人工繁育树鼩部分生理指标检测与比较. 动物学研究, 32(1): 4-10.]

Magari?os AM, McEwen BS, Flugge G, Fuchs E. 1996. Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J Neurosci, 16(10): 3534-3540.

McBrien NA, Norton TT. 1994. Prevention of collagen crosslinking increases form-deprivation myopia in tree shrew. Exp Eye Res, 59(4): 475-486.

McBrien NA, Arumugam B, Metlapally S. 2012. The effect of daily transient +4 D positive lens wear on the inhibition of myopia in the tree shrew. Invest Ophth Vis Sci, 53(3): 1593-1601.

Nie WH, Fu BY, O'Brien PC, Wang JH, Su WT, Tanomtong A, Volobouev V, Ferguson-Smith MA, Yang FT. 2008. Flying lemurs-the 'flying tree shrews'? Molecular cytogenetic evidence for a scandentia-dermoptera sister clade. BMC Biol, 6: 18.

Norton TT. 1999. Animal models of myopia: learning how vision controls the size of the eye. ILAR J, 40(2): 59-77.

Pang QF, Wan XB, Xu AY, Wang ZM, Wang GX, Zhu BY, Zhang XS. 1981. Hepatitis B virus (HBV) infection in the experimental tree shrews (Abstract). J Med Res, (9): 11-12. [庞其方, 万新邦, 胥爱源, 王祖铭, 王桂香, 朱宝友, 张新生. 1981. 乙型肝炎病毒(HBV)感染树鼩的实验研究(摘要). 医学研究通讯, (9): 11-12.]

Park US, Su JJ, Ban KC, Qin LL, Lee EH, Lee YI. 2000. Mutations in the p53 tumor suppressor gene in tree shrew hepatocellular carcinoma associated with hepatitis B virus infection and intake of aflatoxin B1. Gene, 251(1): 73-80.

Pawlik M, Fuchs E, Walker LC, Levy E. 1999. Primate-like amyloid-beta sequence but no cerebral amyloidosis in aged tree shrews. Neurobiol Aging, 20(1): 47-51.

Peng YZ, Ye ZZ, Zou RJ, Wang YX, Tian BP, Ma YY, Shi LM. 1991. Biology of Chinese Tree Shrews [M]. Kunming: Yunnan Science and Technology Press. [彭燕章, 叶智彰, 邹如金, 王应祥, 田保平, 马原野, 施立明. 1991. 树鼩生物学. 昆明: 云南科技出版社.]

Rao MS, Reddy JK. 1980. Carcinogenicity of 2, 2'-dihydroxy-di-npropylnitrosamine in the tree shrew (Tupaia glis): light and electron microscopic features of pulmonary adenomas. J Natl Cancer Inst, 65(4): 835-840.

Reddy JK, Svoboda DJ, Rao MS. 1976. Induction of liver tumors by aflatoxin B1 in the tree shrew (Tupaia glis), a nonhuman primate. Cancer Res, 36(1): 151-160.

Schmitz J, Ohme M, Zischler H. 2000. The complete mitochondrial genome of Tupaia belangeri and the phylogenetic affiliation of scandentia to other eutherian orders. Mol Biol Evol, 17(9): 1334-1343.

Schwaier A. 1979. Tupaias (tree shrews)-a new animal model for gallstone research. Res Exp Med (Berl), 176(1): 15-24.

Shen PQ, Zheng H, Liu RW, Chen LL, Li B, He BL, Li JT, Ben KL, Cao YM, Jiao JL. 2011. Progress and prospect in research on laboratory tree shrew in China. Zool Res, 32 (1): 109-114. [沈培清, 郑红, 刘汝文, 陈丽玲, 李波, 何保丽, 李进涛, 贲昆龙, 曹筱梅, 角建林. 2011. 中国树鼩实验动物化研究进展和展望. 动物学研究, 32(1): 109-114.]

Siegwart JT, Norton TT. 2002. The time course of changes in mRNA levels in tree shrew sclera during induced myopia and recovery. Invest Ophthalmol Vis Sci, 43(7): 2067-2075.

Su JJ, Yan RQ, Gan YQ, Zhou DN, Huang DR, Huang GH. 1986. A Study of experimental infection by human hepatitis B virus (HBV) in adult tree shrew. Shanghai Lab Anim Sci, 6(4): 193-198. [苏建家, 严瑞琪, 甘友全, 周德南, 黄定瑞, 黄国华. 1986. 人乙型肝炎病毒实验感染成年树鼩的研究. 上海实验动物科学, 6(4): 193-198.]

Su JJ, Ban KC, Li Y, Qin LL, Wang HY, Yang C, Ou C, Duan XX, Lee YL, Yang RQ. 2004. Alteration of p53 and p21 during hepatocarcinogenesis in tree shrews. World J Gastroenterol, 10(24): 3559-3563.

Vollmayr B, Mahlstedt MM, Henn FA. 2007. Neurogenesis and depression: what animal models tell us about the link. Eur Arch Psychiatry Clin Neurosci, 257: 300-303.

Wagner JD, Cline JM, Shadoan MK, Bullock BC, Rankin SE, Cefalu WT. 2001. Naturally occurring and experimental diabetes in cynomolgus monkeys: a comparison of carbohydrate and lipid metabolism and islet pathology. Toxicol Pathol, 29: 142-148.

Walter E, Keist R, Niederost B, Pult I, Blum HE. 1996. Hepatitis B virus infection of tupaia hepatocytes in vitro and in vivo. Hepatology, 24(1): 1-5.

Wang HP, Zhou YX, Yao ZQ, Hong S, Li GY. 1997. Preliminary study of HCV infected Adult tree shrews. J Fourth Mili Med Univ, 18(4): 375-376. [王海平, 周永兴, 姚志强, 洪沙, 李光玉. 1997. 成年树鼩实验感染丙型肝炎病毒的初步研究. 第四军医大学学报, 18(4): 375-376.]

Wang J, Zhou QX, Tian M, Yang YX, Xu L. 2011. Tree shrew models: a chronic social defeat model of depression and a one-trial captive conditioning model of learning and memory. Zool Res, 32(1): 24-30.

Wang J, Xu XL, Ding ZY, Mao RR, Zhou QX, Lü LB, Wang LP, Zhang C, Xu L, Yang YX. 2013. Basal physiological indexes in domesticated tree shrews. Zool Res, 34 (in press)

Wang J, Zhou QX, Lü LB, Xu L, Yang YX. 2012. A depression model of social defeat etiology using tree shrews. Zool Res, 33(1): 92-98. [王静, 周启心, 吕龙宝, 徐林, 杨跃雄. 2012. 社会竞争失败病因学的抑郁症树鼩模型. 动物学研究, 33(1): 92-98.]

Wang XX, Li JX, Wang WG, Sun XM, He CY, Dai JJ. 2011. Preliminary investigation of viruses to the wild tree shrews (Tupaia belangeri chinese). Zool Res, 32(1): 66-69. [王新兴, 李婧潇, 王文广, 孙晓梅, 何春艳, 代解杰. 2011. 野生中缅鼩病毒携带情况的初步调查. 动物学研究, 32(1): 66-69.]

Wang YX. 1987. Taxonomic research on Burma-Chinese tree shrew, Tupaia belangeri (Wagner), from Southern China. Zool Res, 8(3): 213-230. [王应祥. 1987. 中国树鼩的分类研究. 动物学研究, 8(3): 213-230.]

Wu X, Chang Q, Zhang Y, Zou X, Chen L, Zhang L, Liang B. 2013. Relationships between body weight, fasting blood glucose, sex, and age in tree shrews (Tupaia belangeri chinensis). J Anim Physiol Anim Nutr, in press.

Xia H, Wang C, Zhang H, He B, Jiao J, Chen C. 2012. Characterization of spontaneous breast tumor in tree shrews (Tupaia belangeri chinenesis). Zool Res, 33(1): 55-59.

Xian S, Huang S, Su JJ, Qin YF, Ou C, Luo ZJ, Wei MY. 2000. A study on experimental diabetes animal models in tree shrews induced by streptozotocin. J Guangxi Med Univ, 17(6): 945-948. [冼苏, 黄松, 苏建家, 秦映芬, 欧超, 罗佐杰, 韦敏怡. 2000. 链脲佐菌素诱导树鼩糖尿病动物模型研究. 广西医科大学学报, 17(6): 945-948.]

Xie ZC, Riezu-Boj JI, Lasarte JJ, Guillen J, Su JH, Civeira MP, Prieto J. 1998. Transmission of hepatitis C virus infection to tree shrews. Virology, 244(2): 513-520.

Xu L. 2011. Aniaml models of human diseases. Zool Res, 32(1): 1-3. [徐林. 2011. 人类疾病的动物模型. 动物学研究, 32(1): 1-3.]

Xu L, Fan Y, Jiang XL, Yao YG. 2013. Molecular evidence on the phylogenetic position of tree shrew (Tupia belangeri). Zool Res, 34 (2):70-76. [许凌, 范宇, 蒋学龙, 姚永刚. 2013. 树鼩进化分类地位的分子证据. 动物学研究, 34 (2):70-76.]

Xu L, Chen SY, Nie WH, Jiang XL, Yao YG. 2012. Evaluating the phylogenetic position of Chinese Tree Shrew (Tupaia belangeri chinensis) based on complete mitochondrial genome: implication for using tree shrew as an alternative experimental animal to primates in biomedical research. J Genet Genomics, 39(3): 131-137.

Yamashita A, Fuchs E, Taira M, Yamamoto K, Hayashi M. 2012. Somatostatin-immunoreactive senile plaque-like structures in the frontal cortex and nucleus accumbens of aged tree shrews and Japanese macaques. J Med Primat, 41(3): 147–157.

Yan H, Zhong GC, Xu GW, He WH, Jing ZY, Gao ZC, Huang Y, Qi YH, Peng B, Wang HM, Fu L, Song M, Chen P, Gao WQ, Ren BJ, Sun YY, Cai T, Feng XF, Sui JH, Li WH. 2012. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife, 1: e00049.

Yan RQ, Su JJ, Chen ZY, Liu YG, Gan YQ, Zhou DN. 1984. A preliminary study on experimental infection of human hepatitis B virus in adult tree shrews. J Guangxi Med Univ, 1(1): 10-15. [严瑞琪, 苏建家, 陈志英, 刘由庚, 甘友全, 周德南. 1984. 人乙型肝炎病毒实验感染成年树鼩的初步研究. 广西医学院学报, 1(1): 10-15.]

Yan RQ, Su JJ, Huang DR, Gan YC, Yang C, Huang GH. 1996. Human hepatitis B virus and hepatocellular carcinoma. II. Experimental induction of hepatocellular carcinoma in tree shrews exposed to hepatitis B virus and aflatoxin B1. J Cancer Res Clin Oncol, 122(5): 289-295. ang F, Cao J, Zhang JJ, Wang Q, Su JJ, Yang C, Ou C, Shi JL, Wang DP, Li Y. 2009. Long-term observation of hepatitis B virus (HBV) replication in new-born tree shrews inoculated with HBV. Chn J Hepatol, 17(8): 580-584. [杨芳, 曹骥, 张晶晶, 王琦, 苏建家, 杨春, 欧超, 史俊林, 汪多平, 李瑗. 2009. 新生期树鼩接种人乙型肝炎病毒的长期实验观察. 中华肝脏病杂志, 17(8): 580-584.]

Zambello E, Fuchs E, Abumaria N, Rygula R, Domenici E, Caberlotto L. 2010. Chronic psychosocial stress alters NPY system: different effects in rat and tree shrew. Prog Neuropsychopharmacol Biol Psychiatry, 34(1): 122-130.

Zhan MY, Liu CX, Li CM, Zhang WY, Zhu C, Pang QF, Zhao TX, Wang CA, Wang JL, Yu CY, Li SF, Tong ZG, Lin ZH, Niu JQ. 1981. A preliminary study of hepatitis A virus in Chinese Tupaia. Acta Acad Med Sin, 3(3): 148-152. [詹美云, 刘崇相, 李成明, 张文英, 朱纯, 庞其方, 赵同兴, 王长安, 王金利, 余昌晏, 李寿复, 佟智功, 林尊慧, 牛京勤. 1981. 甲型肝炎病毒感染树鼩的初步研究. 中国医学科学院学报, 3(3): 148-152.]